Sandbox ASBMB 25

Influenza neuraminidase

Influenza neuraminidase is a glycoprotein in the influenza virus membrane. Before an infected cell can release the virus into its surroundings to infect new cells, neuraminidase must cleave sialic acid from both virus and cellular glycoproteins.

Because of its important role in virus infectivity, several anti-viral drugs have been designed to target neuraminidase, including oseltamivir (Tamiflu) and zanamivir (Relenza). Tamiflu binding to neuraminidase moves glutamate 276 towards histidine 274, making more room for Tamiflu to bind tightly (PDB entry 2hu4). But, in a common mutant (H274Y), a larger tyrosine replaces the smaller histidine 274, preventing glutamate 276 from moving to make room for Tamiflu binding, resulting in weaker drug binding and thus resistance (PDB entry 3cl0). Luckily the H274Y neuraminidase mutant is still susceptible to Relenza, which is smaller than Tamiflu.

{Which neuraminidase residue moves to make room for Tamiflu binding but cannot do so in the H274Y neuraminidase mutant? - histidine 274 - serine 278 + glutamate 276 - tyrosine 274
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